The liver is a multi-functional organ. Its basic functions can be divided into three categories: (1) the vascular functions for storage and filtration of blood, (2) the metabolic functions which are involved with most of the metabolic systems of the body, and (3) the secretory and excretory functions responsible for bile formation. Major activities of the liver include detoxification and elimination of both endogenous and exogenous toxins, deamination of amino acids and formation of urea, regulation of blood sugar through the formation of glycogen, production of plasma proteins, production and secretion of bile, and phagocytosis of particulate matter from the splanchnic (intestinal) circulation.
As a result of liver's many different roles, when the liver is damaged, its various functions are disturbed simultaneously in different combinations, depending on the nature and location of the damage. Liver damage from any source may result in liver regeneration, necrosis (cell death), degeneration, inflammation, fibrosis, or combinations of these processes. Although the liver has great functional reserves, with progressive injury, disruption of liver function can have life-threatening consequences. Cirrhosis, which is a common end-stage liver disease, is one of the top ten causes of death in the Western world.
Despite the significance and potential severity of liver disease, therapeutic approaches are limited. Many types of liver disease are the result of viruses (e.g., hepatitis A, B, C, D, and E), and effective anti-viral therapies are rare and often cause potentially severe side effects. Other liver diseases are the results of previous toxic exposure (such as alcoholic cirrhosis and exposure to toxic plants, or environmental pollutants). In still other cases, liver diseases are the result of poorly understood interplay of various factors, including genetic factors, environmental conditions, and immune system activity (autoimmune hepatitis). No matter what the causes are, therapeutic approaches to liver diseases are complicated by two factors. Since the liver is responsible for detoxification, any use of drugs may increase the burden upon the liver and lead to deterioration of the condition. Furthermore, liver fibrosis, which occurs in many liver diseases and conditions, is generally an irreversible process. Consequently, the usable portion of the liver decreases with the progress of fibrosis, resulting in increasing complications of other organs that rely on liver functions.
Therefore, a pharmaceutical agent for the liver should ideally prevent fibrosis from occurring or progressing. In addition, it is also desirable if the agent does not pose a metabolic burden on the liver, as well as has few or no side effects.
The details of one or more embodiments of the invention are set forth in the description below. Other features or advantages of the present invention will be apparent from the following drawings and detailed description of several embodiments, and also from the appending claims.